chr20-33852179-T-G
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM1BP4_ModerateBS2
The NM_176812.5(CHMP4B):c.586T>G(p.Ser196Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_176812.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHMP4B | NM_176812.5 | c.586T>G | p.Ser196Ala | missense_variant | 4/5 | ENST00000217402.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHMP4B | ENST00000217402.3 | c.586T>G | p.Ser196Ala | missense_variant | 4/5 | 1 | NM_176812.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251496Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135922
GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461884Hom.: 0 Cov.: 32 AF XY: 0.0000124 AC XY: 9AN XY: 727242
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
Cataract 31 multiple types Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 02, 2019 | This sequence change replaces serine with alanine at codon 196 of the CHMP4B protein (p.Ser196Ala). The serine residue is highly conserved and there is a moderate physicochemical difference between serine and alanine. This variant is present in population databases (rs765835212, ExAC 0.009%). This variant has not been reported in the literature in individuals with CHMP4B-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at